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Published on: December 4, 2018
Nfe2l3 (Nrf3) deficiency predisposes mice to T-cell lymphoblastic lymphoma
Grégory Chevillard1, Marilene Paquet, Volker Blank
1Lady Davis Institute for Medical Research and Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC, Canada.
Abstract:
We have previously generated mice deficient for Nfe213 (NF-E2 p45 related factor 3 or Nrf3), a member of the cap 'n' collar family of basic-leucine zipper transcription factors. To examine whether Nrf3 is involved in chemical-induced carcinogenesis, we exposed the mice to benzo[a]pyrene (B[a]P), a carcinogen found in cigarette smoke. Contrary to wild-type mice, Nrf3-null animals are highly susceptible to B[a]P, exhibiting significantly increased mortality. Pathology analysis of affected tissue sections revealed a high incidence of T-cell lymphoblastic lymphoma in B[a]P-treated Nrf3(-/-) mice. Lymphoblastic lymphoma occasionally metastasized into the lung as demonstrated by perivascular malignant lymphocytic infiltration. Together, our studies show that the absence of Nrf3 predisposes mice to lymphoma development, suggesting a protective role of this transcription factor in hematopoietic malignancies. Our data demonstrate the first in vivo function of Nrf3 and its link to tumor development. Nrf3-deficient mice may serve as a preclinical mouse model to study carcinogen-induced lymphomagenesis.
Insights
Mice lacking the Nrf3 transcription factor showed increased susceptibility to cancer when exposed to benzo[a]pyrene. This suggests Nrf3 plays a protective role against chemical-induced lymphoma development.
Area of Science:
- Molecular Biology
- Toxicology
- Oncology
Background:
- NF-E2 p45 related factor 3 (Nrf3) is a transcription factor belonging to the cap 'n' collar family.
- The in vivo function of Nrf3, particularly in chemical carcinogenesis, remains largely unexplored.
Purpose of the Study:
- To investigate the role of Nrf3 in chemical-induced carcinogenesis.
- To determine if Nrf3 deficiency influences susceptibility to benzo[a]pyrene (B[a]P)-induced tumors.
Main Methods:
- Generation of Nrf3-deficient (Nrf3(-/-)) mice.
- Exposure of wild-type and Nrf3(-/-) mice to the carcinogen benzo[a]pyrene (B[a]P).
- Pathological analysis of tissues to assess tumor incidence and type.
Main Results:
- Nrf3(-/-) mice exhibited significantly higher mortality rates compared to wild-type mice after B[a]P exposure.
- A high incidence of T-cell lymphoblastic lymphoma was observed in B[a]P-treated Nrf3(-/-) mice.
- Metastasis of lymphoblastic lymphoma to the lungs was noted in some Nrf3-deficient mice.
Conclusions:
- The absence of Nrf3 predisposes mice to lymphoma development, indicating a protective role in hematopoietic malignancies.
- Nrf3 plays a crucial role in preventing carcinogen-induced lymphomagenesis.
- Nrf3-deficient mice represent a valuable preclinical model for studying lymphoma development.
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